This project seeks to utilize state-of-the-art molecular cytogenetic techniques to determine the frequency and persistence of stable cytogenetic damage in peripheral T lymphocytes of victims of the Chernobyl nuclear reactor accident. the subjects involved in this study fall into two groups: those who received high whole-body doses (ranging from ~0.8 to ~6 Gy), and those who were exposed more slowly (over a period of one or a few days) and received ~0.25 Gy. Fluorescence in situ hybridization of chromosome-specific composite DNA probes ("chromosome painting") will be used to measure the frequency of stable chromosome aberrations, i.e. translocations. These results will be validated against the conventional method of G-banding. In a cross-sectional component of this study, 60 people whose exposures range from 0 (matched controls) to the highest surviving doses will be examined. Accurate exposure estimates will be made and used as a benchmark against which the results of the glycophorin A, HPRT, and germinal mutation portions of this Program Project will be compared. The dosimetry will also be used to guide the selection of subjects for a longitudinal component of this study. Here, 16 subjects who span the dose range will be examined for five consecutive years. The proposed work will lead to a greatly improved understanding of the temporal stability of various cytogenetic anomalies (particularly translocations), the extent of clonal expansion following radiation exposure, the effects of dose on translocation stability nd clonal expansion, and the utility of chromosome painting as a reliable and effective biodosimeter following accidental radiation exposure. In conjunction with the GPA, HPRT, and germinal mutation efforts of this Program Project, this work will lead to a greatly increased understanding of the long-term effects of human exposure to ionizing radiation.